Fan Jiye, Tian Liying, Li Manli, Huang Shu-Hong, Zhang Jing, Zhao Baohua
Department of Biochemistry and Molecular Biology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, PR China.
Department of Pharmacy, Hebei Chemical and Pharmaceutical College, Shijiazhuang, Hebei 050026, PR China.
Oncotarget. 2017 Nov 21;8(64):108238-108248. doi: 10.18632/oncotarget.22602. eCollection 2017 Dec 8.
MARCH8 belongs to a family of membrane-associated RING-CH (MARCH) ubiquitin ligases. The functions of MARCH8 have been thoroughly investigated but its mechanism of action remains unknown. In this study, we detected the expression of MARCH8 protein in NSCLC samples and identified MARCH8 mRNA expression through a TCGA database. In addition, we analyzed the correlation between MARCH8 and the clinical characteristics of NSCLC patients and their prognosis.(www.kmplot.com). The roles of MARCH8 in proliferation, migration, and metastasis were further explored through ectopic expression analysis and western blot analysis; its mechanism of expressionwas also explored. We discovered that MARCH8 was downregulated in NSCLC tissues compared to adjacent normal lung tissues. Overexpression of MARCH8 inhibited NSCLC cell proliferation and metastasis via the PI3K and mTOR signaling pathways; this also increased apoptosis of A549 and H1299 cells. Our results indicated that MARCH8 plays crucial roles in NSCLC against carcinogenesis and progression; therefore, MARCH8 might be a predictive factor and an attractive therapeutic target for NSCLC patients.
MARCH8属于膜相关RING-CH（MARCH）泛素连接酶家族。MARCH8的功能已得到充分研究，但其作用机制仍不清楚。在本研究中，我们检测了非小细胞肺癌（NSCLC）样本中MARCH8蛋白的表达，并通过癌症基因组图谱（TCGA）数据库确定了MARCH8信使核糖核酸（mRNA）的表达。此外，我们分析了MARCH8与NSCLC患者临床特征及其预后之间的相关性（www.kmplot.com）。通过异位表达分析和蛋白质免疫印迹分析进一步探讨了MARCH8在增殖、迁移和转移中的作用；还探讨了其表达机制。我们发现，与相邻正常肺组织相比，NSCLC组织中MARCH8表达下调。MARCH8的过表达通过磷脂酰肌醇-3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白（mTOR）信号通路抑制NSCLC细胞增殖和转移；这也增加了A549和H1299细胞的凋亡。我们的结果表明，MARCH8在NSCLC的发生和进展中起关键作用；因此，MARCH8可能是NSCLC患者的一个预测因素和有吸引力的治疗靶点。
